Procedural-Related Bleeding in Hospitalized Patients With Liver Disease (PROC-BLeeD): An International, Prospective, Multicenter Observational Study.

BACKGROUND & AIMS: Hospitalized patients with cirrhosis frequently undergo multiple procedures. The risk of procedural-related bleeding remains unclear, and management is not standardized. We conducted an international, prospective, multicenter study of hospitalized patients with cirrhosis undergoing nonsurgical procedures to establish the incidence of procedural-related bleeding and to identify bleeding risk factors. METHODS: Hospitalized patients were prospectively enrolled and monitored until surgery, transplantation, death, or 28 days from admission. The study enrolled 1187 patients undergoing 3006 nonsurgical procedures from 20 centers. RESULTS: A total of 93 procedural-related bleeding events were identified. Bleeding was reported in 6.9% of patient admissions and in 3.0% of the procedures. Major bleeding was reported in 2.3% of patient admissions and in 0.9% of the procedures. Patients with bleeding were more likely to have nonalcoholic steatohepatitis (43.9% vs 30%) and higher body mass index (BMI; 31.2 vs 29.5). Patients with bleeding had a higher Model for End-Stage Liver Disease score at admission (24.5 vs 18.5). A multivariable analysis controlling for center variation found that high-risk procedures (odds ratio [OR], 4.64; 95% confidence interval [CI], 2.44-8.84), Model for End-Stage Liver Disease score (OR, 2.37; 95% CI, 1.46-3.86), and higher BMI (OR, 1.40; 95% CI, 1.10-1.80) independently predicted bleeding. Preprocedure international normalized ratio, platelet level, and antithrombotic use were not predictive of bleeding. Bleeding prophylaxis was used more routinely in patients with bleeding (19.4% vs 7.4%). Patients with bleeding had a significantly higher 28-day risk of death (hazard ratio, 6.91; 95% CI, 4.22-11.31). CONCLUSIONS: Procedural-related bleeding occurs rarely in hospitalized patients with cirrhosis. Patients with elevated BMI and decompensated liver disease who undergo high-risk procedures may be at risk to bleed. Bleeding is not associated with conventional hemostasis tests, preprocedure prophylaxis, or recent antithrombotic therapy.

MAFLD predicts cardiovascular disease risk better than MASLD.

BACKGROUND AND AIM: Metabolic dysfunction-associated steatotic liver disease (MASLD) has been proposed as an alternative for the validated definition of metabolic dysfunction-associated fatty liver disease (MAFLD). We compared the abilities of MAFLD and MASLD to predict the risk of atherosclerotic cardiovascular disease (ASCVD). METHODS: Six thousand and ninety six participants from the 2017 to 2020 National Health and Nutrition Examination Survey cohort who received a thorough medical health check-up were chosen for the study. The associations between fatty liver status and coronary risk surrogates, such as 10-year ASCVD risk and self-reported cardiovascular events, were analysed. RESULTS: MAFLD and MASLD were identified in 2911 (47.7%) and 2758 (45.2%) patients, respectively. MAFLD (odds ratio [OR]: 2.14, 95% confidence interval [CI], 1.78-2.57, p < .001) was more strongly independently associated with high ASCVD risk than MASLD (OR: 1.82, 95% CI, 1.52-2.18, p < .001) was in comparison with the absence of each condition. However, compared with MAFLD, MASLD alone was not associated with increased ASCVD risk. Multiple logistic regression revealed that MAFLD alone was significantly more strongly associated with a high risk of ASCVD (OR: 2.82; 95% CI: 1.13-7.01; p < .03) than MASLD alone. CONCLUSIONS: Although both MAFLD and MASLD were associated with different ASCVD risks, MAFLD predicted the ASCVD risk better than MASLD. The higher predictive ability of MAFLD compared to MASLD was attributed to metabolic dysfunction rather than moderate alcohol use.

From Liver to Brain: How MAFLD/MASLD Impacts Cognitive Function.

Metabolic dysfunction-associated fatty liver disease or metabolic dysfunction-associated steatotic liver disease (MAFLD/MASLD), is a common chronic liver condition affecting a substantial global population. Beyond its primary impact on liver function, MAFLD/MASLD is associated with a myriad of extrahepatic manifestations, including cognitive impairment. The scope of cognitive impairment within the realm of MAFLD/MASLD is a matter of escalating concern. Positioned as an intermediate stage between the normal aging process and the onset of dementia, cognitive impairment manifests as a substantial challenge associated with this liver condition. Insights from studies underscore the presence of compromised executive function and a global decline in cognitive capabilities among individuals identified as being at risk of progressing to liver fibrosis. Importantly, this cognitive impairment transcends mere association with metabolic factors, delving deep into the intricate pathophysiology characterizing MAFLD/MASLD. The multifaceted nature of cognitive impairment in the context of MAFLD/MASLD is underlined by a spectrum of factors, prominently featuring insulin resistance, lipotoxicity, and systemic inflammation as pivotal contributors. These factors interplay within the intricate landscape of MAFLD/MASLD, fostering a nuanced understanding of the links between hepatic health and cognitive function. By synthesizing the available evidence, exploring potential mechanisms, and assessing clinical implications, the overarching aim of this review is to contribute to a more complete understanding of the impact of MAFLD/MASLD on cognitive function.

Underlying Mechanisms behind the Brain-Gut-Liver Axis and Metabolic-Associated Fatty Liver Disease (MAFLD): An Update.

Metabolic-associated fatty liver disease (MAFLD) includes several metabolic dysfunctions caused by dysregulation in the brain-gut-liver axis and, consequently, increases cardiovascular risks and fatty liver dysfunction. In MAFLD, type 2 diabetes mellitus, obesity, and metabolic syndrome are frequently present; these conditions are related to liver lipogenesis and systemic inflammation. This study aimed to review the connection between the brain-gut-liver axis and MAFLD. The inflammatory process, cellular alterations in hepatocytes and stellate cells, hypercaloric diet, and sedentarism aggravate the prognosis of patients with MAFLD. Thus, to understand the modulation of the physiopathology of MAFLD, it is necessary to include the organokines involved in this process (adipokines, myokines, osteokines, and hepatokines) and their clinical relevance to project future perspectives of this condition and bring to light new possibilities in therapeutic approaches. Adipokines are responsible for the activation of distinct cellular signaling in different tissues, such as insulin and pro-inflammatory cytokines, which is important for balancing substances to avoid MAFLD and its progression. Myokines improve the quantity and quality of adipose tissues, contributing to avoiding the development of MAFLD. Finally, hepatokines are decisive in improving or not improving the progression of this disease through the regulation of pro-inflammatory and anti-inflammatory organokines.

Metabolic dysfunction: The silenced connection with fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) represents a global public health burden. Despite the increase in its prevalence, the disease has not received sufficient attention compared to the associated diseases such as diabetes mellitus and obesity. In 2020 it was proposed to rename NAFLD to metabolic dysfunction-associated fatty liver disease (MAFLD) in order to recognize the metabolic risk factors and the complex pathophysiological mechanisms associated with its development. Furthermore, along with the implementation of the proposed diagnostic criteria, the aim is to address the whole clinical spectrum of the disease, regardless of BMI and the presence of other hepatic comorbidities. As would it be expected with such a paradigm shift, differing viewpoints have emerged regarding the benefits and disadvantages of renaming fatty liver disease. The following review aims to describe the way to the MAFLD from a historical, pathophysiological and clinical perspective in order to highlight why MAFLD is the approach to follow.

Synergistic Effect of Biejia-Ruangan on Fibrosis Regression in Patients With Chronic Hepatitis B Treated With Entecavir: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial.

BACKGROUND: Long-term nucleos(t)ide analogue (NA) treatment can reverse liver fibrosis in chronic hepatitis B (CHB), but its effect on fibrosis regression remains limited. Biejia-Ruangan (BR) has been approved in China as an antifibrotic traditional Chinese medicine drug in patients with chronic liver diseases. A multicenter randomized controlled trial aims to evaluate the effect of BR on fibrosis regression in CHB patients treated with NAs. METHODS: CHB patients with histologically confirmed advanced fibrosis or cirrhosis were randomly assigned to receive entecavir (ETV) (0.5 mg per day) plus BR (2 g 3 times a day) or placebo for 72 weeks. Liver fibrosis regression was defined as a reduction of ≥ 1 point by the Ishak fibrosis stage (IFS). RESULTS: Overall, 500 patients were enrolled in each group as the intention-to-treat population. The rate of fibrosis regression after 72 weeks of treatment was significantly higher in the ETV + BR group (40% vs 31.8%; P = .0069). Among 388 patients with cirrhosis (ie, IFS ≥ 5) at baseline, the rate of cirrhosis reversal (ie, IFS ≤ 4) was significantly higher in the ETV + BR group (41.5% vs 30.7%; P = .0103). CONCLUSIONS: Addition of BR to the current standard treatment with NAs in CHB patients with advanced fibrosis or cirrhosis can improve liver fibrosis regression. CLINICAL TRIALS REGISTRATION: NCT01965418.

Clinical, histological and molecular profiling of different stages of alcohol-related liver disease.

OBJECTIVE: Alcohol-related liver disease (ALD) ranges from never-decompensated ALD (ndALD) to the life-threatening decompensated phenotype, known as alcohol-related hepatitis (AH). A multidimensional study of the clinical, histological and molecular features of these subtypes is lacking. DESIGN: Two large cohorts of patients were recruited in an international, observational multicentre study: a retrospective cohort of patients with ndALD (n=110) and a prospective cohort of patients with AH (n=225). Clinical, analytical, immunohistochemistry and hepatic RNA microarray analysis of both disease phenotypes were performed. RESULTS: Age and mean alcohol intake were similar in both groups. AH patients had greater aspartate amino transferase/alanine amino transferase ratio and lower gamma-glutamyl transferase levels than in ndALD patients. Patients with AH demonstrated profound liver failure and increased mortality. One-year mortality was 10% in ndALD and 50% in AH. Histologically, steatosis grade, ballooning and pericellular fibrosis were similar in both groups, while advanced fibrosis, Mallory-Denk bodies, bilirubinostasis, severe neutrophil infiltration and ductular reaction were more frequent among AH patients. Transcriptome analysis revealed a profound gene dysregulation within both phenotypes when compare to controls. While ndALD was characterised by deregulated expression of genes involved in matrisome and immune response, the development of AH resulted in a marked deregulation of genes involved in hepatocyte reprogramming and bile acid metabolism. CONCLUSIONS: Despite comparable alcohol intake, AH patients presented with worse liver function compared with ndALD patients. Bilirubinostasis, severe fibrosis and ductular reaction were prominent features of AH. AH patients exhibited a more profound deregulation of gene expression compared with ndALD patients.

A Global Survey of Physicians Knowledge About Nonalcoholic Fatty Liver Disease.

BACKGROUND & AIMS: Despite rapidly increasing nonalcoholic fatty liver disease (NAFLD) prevalence, providers' knowledge may be limited. We assessed NAFLD knowledge and associated factors among physicians of different specialties globally. METHODS: NAFLD knowledge surveys containing 54 and 59 questions covering 3 domains (epidemiology/pathogenesis, diagnostics, and treatment) were completed electronically by hepatologists, gastroenterologists (GEs), endocrinologists (ENDOs), and primary care physicians (PCPs) from 40 countries comprising 5 Global Burden of Disease super-regions. Over 24 months, 2202 surveys were completed (488 hepatologists, 758 GEs, 148 ENDOs, and 808 PCPs; 50% high-income Global Burden of Disease super-region, 27% from North Africa and Middle East, 12% Southeast Asia, and 5% South Asian and Latin America). RESULTS: Hepatologists saw the greatest number of NAFLD patients annually: median 150 (interquartile range, 60-300) vs 100 (interquartile range, 35-200) for GEs, 100 (interquartile range, 30-200) for ENDOs, and 10 (interquartile range, 4-50) for PCPs (all P < .0001). The primary sources of NAFLD knowledge acquisition for hepatologists were international conferences (33% vs 8%-26%) and practice guidelines for others (39%-44%). The Internet was the second most common source of NAFLD knowledge for PCPs (28%). NAFLD knowledge scores were higher for hepatologists than GEs: epidemiology, 62% vs 53%; diagnostics, 80% vs 73%; and treatment, 61% vs 58% (P < .0001), and ENDOs scores were higher than PCPs: epidemiology, 70% vs 60%; diagnostics, 71% vs 64%; and treatment, 79% vs 68% (P < .0001). Being a hepatologist or ENDO was associated with higher knowledge scores than a GE or PCP, respectively (P < .05). Higher NAFLD knowledge scores were associated independently with a greater number of NAFLD patients seen (P < .05). CONCLUSIONS: Despite the growing burden of NAFLD, a significant knowledge gap remains for the identification, diagnosis, and management of NAFLD.

Clinical and Patient-Reported Outcomes From Patients With Nonalcoholic Fatty Liver Disease Across the World: Data From the Global Non-Alcoholic Steatohepatitis (NASH)/ Non-Alcoholic Fatty Liver Disease (NAFLD) Registry.

BACKGROUND & AIMS: Globally, nonalcoholic fatty liver disease (NAFLD) is a common cause of chronic liver disease. We assessed the clinical presentation and patient-reported outcomes (PROs) among NAFLD patients from different countries. METHODS: Clinical, laboratory, and PRO data (Chronic Liver Disease Questionnaire-nonalcoholic steatohepatitis [NASH], Functional Assessment of Chronic Illness Therapy-Fatigue, and the Work Productivity and Activity Index) were collected from NAFLD patients seen in real-world practices and enrolled in the Global NAFLD/NASH Registry encompassing 18 countries in 6 global burden of disease super-regions. RESULTS: Across the global burden of disease super-regions, NAFLD patients (n = 5691) were oldest in Latin America and Eastern Europe and youngest in South Asia. Most men were enrolled at the Southeast and South Asia sites. Latin America and South Asia had the highest employment rates (>60%). Rates of cirrhosis varied (12%-21%), and were highest in North Africa/Middle East and Eastern Europe. Rates of metabolic syndrome components varied: 20% to 25% in South Asia and 60% to 80% in Eastern Europe. Chronic Liver Disease Questionnaire-NASH and Functional Assessment of Chronic Illness Therapy-Fatigue PRO scores were lower in NAFLD patients than general population norms (all P < .001). Across the super-regions, the lowest PRO scores were seen in Eastern Europe and North Africa/Middle East. In multivariate analysis adjusted for enrollment region, independent predictors of lower PRO scores included younger age, women, and nonhepatic comorbidities including fatigue (P < .01). Patients whose fatigue scores improved over time experienced a substantial PRO improvement. Nearly 8% of Global NAFLD/NASH Registry patients had a lean body mass index, with fewer metabolic syndrome components, fewer comorbidities, less cirrhosis, and significantly better PRO scores (P < .01). CONCLUSIONS: NAFLD patients seen in real-world practices in different countries experience a high comorbidity burden and impaired quality of life. Future research using global data will enable more precise management and treatment strategies for these patients.

Severe impairment of patient-reported outcomes in patients with chronic hepatitis C virus infection seen in real-world practices across the world: Data from the global liver registry.

Cure of chronic hepatitis C (CHC) can lead to improvement of health-related quality of life and other patient-reported outcomes (PROs). While extensive PRO data for CHC patients who were enrolled in clinical trials are available, similar data for patients seen in real-world practices are scarce. Our aim was to assess PROs of CHC patients enrolled from real-world practices from different regions and to compare them with those enrolled in clinical trials. CHC patients seen in clinical practices and not receiving treatment were enrolled in the Global Liver Registry (GLR). Clinical and PRO (FACIT-F, CLDQ-HCV, WPAI) data were collected and compared with the baseline data from CHC patients enrolled in clinical trials. N = 12,171 CHC patients were included (GLR n = 3146, clinical trial subjects n = 9025). Patients were from 30 countries from 6 out of 7 Global Burden of Disease (GBD) super-regions. Compared with clinical trial enrollees, patients from GLR were less commonly enrolled from High-Income GBD super-region, older, more commonly female, less employed, had more type 2 diabetes, anxiety and clinically overt fatigue but less cirrhosis (all p < 0.001). Out of 15 PRO domain and summary scores, 12 were lower in GLR patients than in subjects enrolled in clinical trials (p < 0.001). In multiple regression models, anxiety, depression, and fatigue were associated with significant PRO impairment in CHC patients (p < 0.05). After adjustment for the clinico-demographic confounders, the association of PRO scores of CHC patients with enrolment settings was no longer significant (all p > 0.05). In conclusion, hepatitis C patients seen in the real-world practices have PRO impairment driven by fatigue and psychiatric comorbidities.

MAFLD: A quick fact check.

Metabolic (dysfunction)-associated fatty liver disease has taken importance during the last two years, given the new criteria for diagnosis compared to the previous criteria used to define non-alcoholic fatty liver disease. Multiple studies have also shown that this definition better adjusts to the pathogenesis and patient characteristics with fatty liver.

Editorial: Acute Hepatitis of Unknown Origin in Children. Is Autoimmunity at Play?

A recent global outbreak of cases of acute hepatitis of unknown origin in children has raised health alerts. Increasing numbers of cases are being reported in most countries, mainly in the United Kingdom (UK). Although the cause remains unknown, several viruses have been isolated from affected children, including adenovirus, severe acute respiratory syndrome coronavirus 2 (SARS­CoV­2), Epstein-Barr virus (EBV), and rhinovirus. Notably, the cause is not from common hepatitis viruses, as serology for hepatitis viruses A, B, C, D, and E has been negative. Current causal hypotheses include possible infection with a new adenovirus variant that affects immunocompetent children, a new pediatric manifestation of COVID-19, or coinfection with enteric adenovirus type F41. This Editorial aims to present current hypotheses regarding the etiology of acute hepatitis of unknown origin in children, including the role of autoimmune hepatitis secondary to viral infection.

Editorial: The Metabolic (Dysfunction) Associated Fatty Liver Disease (MAFLD)-Non-Alcoholic Fatty Liver Disease (NAFLD) Debate: A Forced Consensus and The Risk of a World Divide.

During the past two years, the redefinition of non-alcoholic fatty liver disease (NAFLD) to metabolic dysfunction-associated fatty liver disease (MAFLD) have been endorsed by international societies of hepatology, patient advocacy associations, and stakeholders. More recently, the American Association for the Study of Liver Diseases (AASLD) and the European Association for the Study of the Liver (EASL) have attempted to achieve a consensus. Three main fundamental issues raise concerns regarding the validity of the current consensus process. First, the development of the process and the selection of experts in the consensus panels remain unclear. Second, there is a concern regarding the quantity and quality of the evidence considered by the consensus panels. Third, there has been a lack of input to the consensus panel decisions from the academic and clinical community. This Editorial aims to raise an urgent note of caution regarding the consensus process used by the AASLD and EASL regarding fatty liver disease, to prevent world divide and different global definitions and guidelines from being adopted.

Editorial: Treatment with Dual Incretin Receptor Agonists to Maintain Normal Glucose Levels May Also Maintain Normal Weight and Control Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD).

Worldwide, metabolic dysfunction-associated fatty liver disease (MAFLD) is the most common chronic liver disease. MAFLD is associated with insulin resistance, type 2 diabetes mellitus (T2DM), obesity, hypertension, and dyslipidemia. Early diagnosis and management are vital to improving hepatic and cardiometabolic outcomes. Dietary change, weight loss, and structured exercise are the main treatment approaches for fatty liver disease. Since 2010, several investigational drug treatments failed to achieve regulatory approval due to mixed and unsatisfactory results. Although glucagon-like peptide 1 receptor agonists (GLP1-RAs) showed initial promise as therapeutic agents, metabolic liver damage can recur after monotherapy cessation. Dual incretin receptor agonists target the receptors for glucagon-like peptide 1 (GLP-1) and gastric inhibitory peptide (GIP). Importantly, on May 13, 2022, the US Food and Drug Administration (FDA) approved tirzepatide as the first dual GLP-1 and GIP receptor agonist for the treatment of T2DM. Dual incretin receptor agonists induce weight loss and enhance hepatic lipid metabolism and systemic insulin sensitivity. Insulin resistance and hepatic steatosis are the main contributors to the development of MAFLD. Treatment with dual incretin analogs reduces hepatic steatosis, lobular inflammation, liver cell damage, fibrosis, and total liver triglyceride levels. The availability of dual incretin receptor agonists for patients with MAFLD may result in weight control, normalizing insulin sensitivity, and reducing or even reversing metabolic dysfunction and liver damage. This Editorial aims to provide an update and discuss how treatment with dual incretin receptor agonists may maintain normal glucose levels and weight and control MAFLD.

Identification of Hepatic Dendritic Cells in Liver Biopsies Showing Steatosis in Patients with Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD) Associated with Obesity.

BACKGROUND Metabolic dysfunction-associated fatty liver disease (MAFLD) is now the term used for hepatic steatosis in patients who are overweight or obese, have type 2 diabetes mellitus (T2DM), or evidence of metabolic dysregulation. The prevalence of MAFLD among morbidly obese subjects is 65-93%. Hepatic dendritic cells (hDCs) are antigen-presenting cells that induce T cell-mediated immunity. MAFLD pathogenesis involves numerous immune cell-mediated inflammatory processes, while the particular role of hDCs is yet to be well defined. This study aimed to identify hDCs in liver biopsies from 128 patients with MAFLD associated with obesity. MATERIAL AND METHODS In this cross-sectional study, 128 liver biopsies from 128 patients with MAFLD (diagnosed as presence of hepatic steatosis, plus T2DM, metabolic dysregulation or overweight/obesity) were collected and assessed for CD11c⁺ immunoreactivity degree (CD11c as dendritic cell biomarker), through antigen retrieval, reaction with CD11c antibodies (primary), and marking with diaminobenzidine chromogen. RESULTS Among the 128 patients with MAFLD, 64 (50%) had MAFLD and fibrosis and 72 (56.2%) positively expressed hDCs (CD11c⁺). Among morbidly obese patients, 49 (64.5%) positively expressed hDCs (CD11c⁺) in liver tissue; from patients with obesity grade I- grade II (GI-II), 18 (54.5%) positively expressed hDCs (CD11c⁺) in liver tissue; and from non-obese patients with MAFLD, 5 (26.3%) positively expressed hDCs (CD11c⁺) in liver tissue. CONCLUSIONS hDC expression increases significantly in morbidly obese patients with MAFLD compared with non-obese patients, independent of the degree of fibrosis, suggesting the role of adaptive changes within hDCs in the perpetuation of inflammatory insults in chronic liver diseases.

Liver Injury in COVID-19 Patients with Drugs as Causatives: A Systematic Review of 996 DILI Cases Published 2020/2021 Based on RUCAM as Causality Assessment Method.

Patients with coronavirus disease 19 (COVID-19) commonly show abnormalities of liver tests (LTs) of undetermined cause. Considering drugs as tentative culprits, the current systematic review searched for published COVID-19 cases with suspected drug-induced liver injury (DILI) and established diagnosis using the diagnostic algorithm of RUCAM (Roussel Uclaf Causality Assessment Method). Data worldwide on DILI cases assessed by RUCAM in COVID-19 patients were sparse. A total of 6/200 reports with initially suspected 996 DILI cases in COVID-19 patients and using all RUCAM-based DILI cases allowed for a clear description of clinical features of RUCAM-based DILI cases among COVID-19 patients: (1) The updated RUCAM published in 2016 was equally often used as the original RUCAM of 1993, with both identifying DILI and other liver diseases as confounders; (2) RUCAM also worked well in patients treated with up to 18 drugs and provided for most DILI cases a probable or highly probable causality level for drugs; (3) DILI was preferentially caused by antiviral drugs given empirically due to their known therapeutic efficacy in other virus infections; (4) hepatocellular injury was more often reported than cholestatic or mixed injury; (5) maximum LT values were found for alanine aminotransferase (ALT) 1.541 U/L and aspartate aminotransferase (AST) 1.076 U/L; (6) the ALT/AST ratio was variable and ranged from 0.4 to 1.4; (7) the mean or median age of the COVID-19 patients with DILI ranged from 54.3 to 56 years; (8) the ratio of males to females was 1.8-3.4:1; (9) outcome was favorable for most patients, likely due to careful selection of the drugs and quick cessation of drug treatment with emerging DILI, but it was fatal in 19 patients; (10) countries reporting RUCAM-based DILI cases in COVID-19 patients included China, India, Japan, Montenegro, and Spain; (11) robust estimation of the percentage contribution of RUCAM-based DILI for the increased LTs in COVID-19 patients is outside of the current scope. In conclusion, RUCAM-based DILI with its clinical characteristics in COVID-19 patients and its classification as a confounding variable is now well defined, requiring a new correct description of COVID-19 features by removing DILI characteristics as confounders.

Editorial: International Consensus Recommendations to Replace the Terminology of Non-Alcoholic Fatty Liver Disease (NAFLD) with Metabolic-Associated Fatty Liver Disease (MAFLD).

In 2020, international consensus guidelines recommended the renaming of non-alcoholic fatty liver disease (NAFLD) to metabolic-associated fatty liver disease (MAFLD), supported by diagnostic criteria. MAFLD affects up to 25% of the global population. However, the rates of MAFLD are likely to be underestimated due to the increasing prevalence of type 2 diabetes mellitus (T2DM) and obesity. Within the next decade, MAFLD has been projected to become a major cause of cirrhosis and hepatocellular carcinoma (HCC) worldwide, as well as the most common indication for liver transplantation in the US. This transition in terminology and clinical criteria may increase momentum and clinical evidence at multiple levels, including patient diagnosis, management, and care, and provide the basis for new research areas and clinical development for therapeutics. The diagnostic criteria for MAFLD are practical, simple, and superior to the existing NAFLD criteria for identifying patients at increased risk of developing progressive liver disease. This Editorial aims to present the historical evolution of the terminology for fatty liver disease and the advantages of diagnosis, patient management, and future research on MAFLD.

A Review of the Increasing Prevalence of Metabolic-Associated Fatty Liver Disease (MAFLD) in Children and Adolescents Worldwide and in Mexico and the Implications for Public Health.

Non-alcoholic fatty liver disease (NAFLD) affects almost a quarter of the world's population and is the most common cause of chronic liver disease in children and adolescents. The recent proposal to replace the terminology of NAFLD with metabolic-associated fatty liver disease (MAFLD) aims to reflect the pathophysiology and risk factors for this disease. Importantly, the risk factors for MAFLD may be prenatal, such as genetic factors, or postnatal, such as obesity and insulin resistance. MAFLD is increasingly recognized in children and adolescents. Early diagnosis and identification of high-risk individuals with type 2 diabetes mellitus and metabolic syndrome is important. The diagnosis and management of MAFLD in children and adolescents should follow international clinical guidelines, such as those from the American Diabetes Association (ADA) and the International Society for Pediatric and Adolescent Diabetes (ISPAD). Current guidelines recommend lifestyle and dietary modifications, exercise, screening, individualized patient assessment, and multidisciplinary patient management. This review assesses the revised terminology and discusses the epidemiology, risk factors, pathophysiology, diagnosis, and prevention of MAFLD in children and adolescents worldwide and in Mexico, and also considers the implications for public health.

NAFLD: Challenges and opportunities to address the public health problem in Latin America.

Non-alcoholic fatty liver disease (NAFLD) is reaching epidemic proportions worldwide. Collectively, Latin American countries have some of the highest obesity rates in the world and the fastest-growing prevalence of type 2 diabetes mellitus (T2DM). Since obesity and T2DM are intrinsically linked with NAFLD, epidemiological projections are worrisome. In addition to this adverse epidemiological setting, the region of Latin America faces unique challenges and obstacles to addressing the growing burden of NAFLD. In this article, on the occasion of the International NASH Day on June 10, 2021, we describe the main challenges and opportunities to improve care of people living with NAFLD in Latin America. Among the major challenges to be tackled are: lack of disease awareness, limited educational opportunities for healthcare personnel and general public, health system fragmentation, and lack of effective strategies for the prevention and effective treatment of NAFLD and common comorbidities, namely obesity and T2DM. Wide dissemination of current concepts on NAFLD, and extensive collaboration between scientific societies, governments, non-governmental organizations, pharmaceutical industry, and other stakeholders is urgently needed to advance the NAFLD public health policies agenda that allows us to address this disease with a whole of society approach.

Drug-induced liver injury: A management position paper from the Latin American Association for Study of the liver.

Idiosyncratic drug-induced liver injury (DILI) caused by xenobiotics (drugs, herbals and dietary supplements) is an uncommon cause of liver disease presenting with a wide range of phenotypes and disease severity, acute hepatitis mimicking viral hepatitis to autoimmune hepatitis, steatosis, fibrosis or rare chronic vascular syndromes. Disease severity ranges from asymptomatic liver test abnormalities to acute liver failure. DILI has been traditionally classified in predictable or intrinsic (dose-related) or unpredictable (not dose-related) mechanisms. Few prospective studies are assessing the real prevalence and incidence of hepatotoxicity in the general population. DILI registries represent useful networks used for the study of liver toxicity, aimed at improving the understanding of causes, phenotypes, natural history, and standardized definitions of hepatotoxicity. Although most of the registries do not carry out population-based studies, they may provide important data related to the prevalence of DILI, and also may be useful to compare features from different countries. With the support of the Spanish Registry of Hepatotoxicity, our Latin American Registry (LATINDILI) was created in 2011, and more than 350 DILI patients have been recruited to date. This position paper describes the more frequent drugs and herbs-induced DILI in Latin America, mainly focusing on several features of responsible medicaments. Also, we highlighted the most critical points on the management of hepatotoxicity in general and those based on findings from our Latin American experience in particular.